Dendritic cells are sentinels of the immune system. They originate from a bone marrow progenitor, travel through the blood and are seeded into non-lymphoid tissue, e.g., skin. Dendritic cells capture and process exogenous antigens for presentation as peptide-MHC complexes at the cell surface and then migrate via the blood and afferent lymph to secondary lymph nodes. In the lymph nodes, they interact with T-lymphocytes to facilitate activation of helper and killer T cells (Steinman, R. (1991) Annu. Rev. Immunol. 9:271; Celia et al. (1997) Curr. Opin. Immunol. 9:10).
Dendritic have been named according to their appearance and distribution in the body. For example, dendritic cells located in the epidermis are known as Langerhans cells. Dendritic cells located in the dermis and interstitium are known as interstitial dendritic cells. Blood, veiled, and lymphoid dendritic cells are found, respectively, in the circulatory system, afferent lymph and the lymph nodes. Dendritic cells have further been characterized by lineage, by maturation stage, by functional and phenotypic characteristics of these stages, and by mechanisms involved in their migration and function (Cella et al., supra; Austyn, J. (1996) J. Exp. Med. 183:1287).
Recent work has demonstrated that cholera toxin can act as a potent transcutaneous adjuvant in noninvasive, transcutaneous immunization in mice (Glenn, G. M. et al. Nature(1998) 391: 851). Cholera toxin applied to the surface of the skin stimulates a strong immune response to coadministered antigens such as diphtheria or tetanus toxoids. This method is particularly important given the large skin surface area and the existence of potent immune cells within it (see, e.g., Bos, J. D., Clin. Exp. Immunol., 107 (Suppl. 1), 3-5, 1997).
Studies with cholera toxin suggest that the holotoxin enhances the presentation of soluble peptides on macrophages, however it inhibited intracellular processing of soluble or bacterial antigens. In contrast, the recombinant B subunit enhanced surface presentation of the antigens, but did not inhibit intracellular processing (Matousek, M. P., J. G. Nedrud and C. V. Harding, J. Immunol., 156, 4137-4145, 1996). Animal studies have also demonstrated the potent capacity of dendritic cells to induce anti-tumor immunity (Nestle, F. O. et al. Nature Medicine, 4:328-332, 1998).